C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes

Sci Rep. 2012:2:1016. doi: 10.1038/srep01016. Epub 2012 Dec 21.


Large expansions of a non-coding GGGGCC-repeat in the first intron of the C9orf72 gene are a common cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). G-rich sequences have a propensity for forming highly stable quadruplex structures in both RNA and DNA termed G-quadruplexes. G-quadruplexes have been shown to be involved in a range of processes including telomere stability and RNA transcription, splicing, translation and transport. Here we show using NMR and CD spectroscopy that the C9orf72 hexanucleotide expansion can form a stable G-quadruplex, which has profound implications for disease mechanism in ALS and FTD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • C9orf72 Protein
  • DNA / genetics
  • DNA Repeat Expansion*
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / metabolism
  • G-Quadruplexes*
  • Genotype
  • Humans
  • Nuclear Magnetic Resonance, Biomolecular
  • Proteins / chemistry
  • Proteins / genetics*


  • C9orf72 Protein
  • C9orf72 protein, human
  • Proteins
  • DNA